Abstract
Objectives 1. Evaluate the risk of neonatal lupus erythematosus (NLE), including congenital heart block (CHB), in neonates born to mothers with anti-Ro/SSA antibodies (anti-Ro60/SSA, anti-LA/SSB, and anti-Ro52), who were treated with or without Hydroxychloroquine (HCQ) during pregnancy, which has evidence for safety.[1] 2. Compare patient characteristics, including anti-Ro/SSA titers, and their relationship on rates of NLE.
Methods Prospective cohort study of pregnant adults aged ≥18 years with positive anti-Ro/SSA antibodies, with or without a systemic autoimmune or rheumatic disease (SARD), who were followed in the Obstetrical Rheumatology Clinic at The Ottawa Hospital until 3 months postpartum. Clinical data was extracted independently by 2 reviewers through standardized chart review. The relationship between maternal HCQ use and neonatal outcomes was analyzed descriptively.
Results 31 pregnant women with anti-Ro/SSA positivity were included. Mean age was 34 ± 5. The majority (61.3%) had a SARD, while 38.7% had no diagnosis. 35.5% had isolated anti-Ro60/SSA antibodies, 19.4% had dual positivity, and 38.7% had triple antibody positivity. 74.2% were treated with HCQ, with 78.2% started pre-conception or first trimester and until delivery. Dose of 400mg (39.1%) or 5mg/kg/day (43.5%). NLE occurred in 3 cases overall (10%), each treated with HCQ, and none reported in the non-HCQ group. 2 NLE cases presented with cutaneous NLE and CHB (8.7%), while the other was limited to cutaneous NLE (4.3%). One case of CHB was treated since pre-conception (type 1) and the other (type III) treated only in third trimester. Both diagnosed between 18-24 weeks gestation, with 87.1% screened for CHB between 16-26 weeks. Each case of NLE occurred with triple positive high titer anti-Ro60, anti-Ro52, and anti-La (Figure 1), with high titer anti-LA/SSB showing a statistically significant difference (p=0.004). Only 10% of patients had anti-La/SSB >1,375, yet this accounted for 66.7% of NLE cases.
Conclusion This is the first study to evaluate the rates of NLE in neonates of anti-Ro/SSA positive mothers treated with HCQ. The results are skewed by a patient with type III CHB prior to starting HCQ late in pregnancy. Accounting for this, rates of NLE with HCQ (8.6%) compared to without (12.5%) are more aligned with prior data. Additionally, the few cases of NLE in this study occurred only with triple positive high titer Ro/La antibodies. This may suggest that patients with low titer antibodies do not require the same rigorous screening, or that treatment with HCQ is more effective in this subset of patients in preventing NLE.
References [1.] Clowse M. Ann Rheum Dis 2021;80:817-23.
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